Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There is reliable data available from a pre-natal developmental toxicity study. According to Annex VIII, section 8.7.1, column 2 of Regulation (EC) No 1907/2006 a screening test for reproductive/developmental toxicity does not need to be conducted if a pre-natal developmental toxicity study according to Annex IX, section 8.7.2, is available.

Furthermore, there is reliable data from a 2-year feeding study available focusing on carcinogenicity. This study includes extensive histopathological investigations of all relevant tissues and organs, and among those male and female reproductive organs like testes, ovaries and uterus. There have no adverse effects been observed in the examined reproductive organs. Therefore, according to Annex IX, section 8.7.3, column 1 of Regulation (EC) No 1907/2006, a 2-generation study for reproductive toxicity does not have to be performed.

Short description of key information:

Data waiving - Toxicity to reproduction: Screening

Data waiving - Two-generation study for reproductive toxicity

Justification for selection of Effect on fertility via oral route:

There is data available from a reliable study assessing the pre-natal developmental toxicity of the test substance. According to Annex VIII, section 8.7.1, column 2 of Regulation (EC) No 1907/2006 a screening test for reproductive/developmental toxicity does not need to be conducted if a pre-natal developmental toxicity study according to Annex IX, section 8.7.2, is available.

Additionally, there is reliable data from a 2-year feeding study available focusing on carcinogenicity. This study includes extensive histopathological investigations of all relevant tissues and organs, and among those male and female reproductive organs like testes, ovaries and uterus. There have no adverse effects been observed in the examined reproductive organs. Therefore, according to Annex IX, section 8.7.3, column 1 of Regulation (EC) No 1907/2006, a 2-generation study for reproductive toxicity does not have to be performed.

Justification for selection of Effect on fertility via inhalation route:

There is data available from a reliable study assessing the pre-natal developmental toxicity of the test substance. According to Annex VIII, section 8.7.1, column 2 of Regulation (EC) No 1907/2006 a screening test for reproductive/developmental toxicity does not need to be conducted if a pre-natal developmental toxicity study according to Annex IX, section 8.7.2, is available.

Additionally, there is reliable data from a 2-year feeding study available focusing on carcinogenicity. This study includes extensive histopathological investigations of all relevant tissues and organs, and among those male and female reproductive organs like testes, ovaries and uterus. There have no adverse effects been observed in the examined reproductive organs. Therefore, according to Annex IX, section 8.7.3, column 1 of Regulation (EC) No 1907/2006, a 2-generation study for reproductive toxicity does not have to be performed.

Justification for selection of Effect on fertility via dermal route:

There is data available from a reliable study assessing the pre-natal developmental toxicity of the test substance. According to Annex VIII, section 8.7.1, column 2 of Regulation (EC) No 1907/2006 a screening test for reproductive/developmental toxicity does not need to be conducted if a pre-natal developmental toxicity study according to Annex IX, section 8.7.2, is available.

Additionally, there is reliable data from a 2-year feeding study available focusing on carcinogenicity. This study includes extensive histopathological investigations of all relevant tissues and organs, and among those male and female reproductive organs like testes, ovaries and uterus. There have no adverse effects been observed in the examined reproductive organs. Therefore, according to Annex IX, section 8.7.3, column 1 of Regulation (EC) No 1907/2006, a 2-generation study for reproductive toxicity does not have to be performed.

Effects on developmental toxicity

Description of key information

Pre-natal developmental toxicity (comparable to OECD 414), mouse, GD6-15: NOAELmat = 2 mg/kg bw/day, NOAELembryotox = 2 mg/kg bw/day, NOAELtera ≥ 600 mg/kg bw/day;

Pre-natal developmental toxicity (comparable to OECD 414), rabbit, GD6-18: NOAELmat = 2 mg/kg bw/day, NOAELembryotox ≥ 300 mg/kg bw/day, NOAELtera = 2 mg/kg bw/day;

Pre-natal developmental toxicity (comparable to OECD 414), rat, GD6-15: NOAELmat, embryotox, tera ≥ 600 mg/kg bw/day

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
2 mg/kg bw/day
Study duration:
subacute
Species:
other: mice and rabbits
Quality of whole database:
The available information comprise adequate and reliable studies (Klimisch score 2) and are thus sufficient to fulfil the standard information requirements set out in Annex IX, section 8.7.2 of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Quality of whole database:
Reliable data via the oral route are available.
Additional information

There is reliable data available from a pre-natal developmental toxicity study that has been published in detail (Palmer et al, 1975a; Palmer et al., 1975b) and been reviewed by Greim et al. (1994). In this study rats, mice and rabbits were treated during the phase of organogenesis (i.e. GD6-15 for mice and rats and GD6-18 for rabbits).

In mice embryotoxicity in form of high incidence of litter losses was observed at 300 mg/kg bw/day, therefore the NOAEL for embryotoxicity was 2 mg/kg bw/day. Due to a disadvantageous choice of dose levels in this study this NOAEL is much lower than actually to be expected. However, this effect was observed at unequivocally maternally toxic doses, reflected by intrauterine resorptions, loss of body weight, and clinical signs; the maternal NOAEL was determined as 2 mg/kg bw/day, as well.

In rabbits, maternal toxicity manifested as mortality in the dams starting already at 300 mg/kg bw/day, the maternal NOAEL was determined as 2 mg/kg bw/day. No embryotoxicity was observed except that related to mortality of the dams, therefore a NOAELembryotoxicity ≥ 300 mg/kg bw/day was determined, due to the lack of surviving dams for assessment at the highest dose. A higher incidence of minor skeletal abnormalities was observed in the offspring at 300 mg/kg bw/day, accordingly the NOAEL for teratogenicity was determined to be 2 mg/kg bw/day. Comparable to mice, all kinds of developmental toxicity observed in rabbits were unequivocally related to maternal toxicity.

In contrast, no toxicity was observed in rats at all, neither in the dams nor in the offspring, a NOAEL ≥ 600 mg/kg bw/day was derived for maternal and developmental toxicity.

Justification for selection of Effect on developmental toxicity: via oral route:

No study was selected since three key studies are available investigating developmental toxicity of the registered substance in three different species.

Justification for selection of Effect on developmental toxicity: via inhalation route:

Reliable data via the oral route are available.

Justification for classification or non-classification

The data from the pre-natal developmental toxicity study demonstrates developmental toxicity in mice and rabbits, but only at unequivocally maternally toxic doses as demonstrated by intrauterine resorptions in the mice and even mortality of the dams in the rabbits. In rats, no adverse effects were observed, at all.

 

Therefore, Sulfonic acids, C14-16 (even numbered)-alkane hydroxy and C14-16 (even numbered)-alkene, sodium salts does not have to be classified for toxicity to reproduction according to the criteria of EU Directive 67/548/EEC or Regulation (EC) No 1272/2008.